Slideshare uses cookies to improve functionality and performance, and to provide you with relevant advertising. If you continue browsing the site, you agree to the use of cookies on this website. See our User Agreement and Privacy Policy.

Slideshare uses cookies to improve functionality and performance, and to provide you with relevant advertising. If you continue browsing the site, you agree to the use of cookies on this website. See our Privacy Policy and User Agreement for details.

11.
Contribution due to terminating ribosomes depends
on the end-to-end distance and the production rate
↵ = ↵o c = ↵o(c1 + cR)
initiation rate
R
r
The probability to end up in the
reaction volume is ∝ r/R
J
current of the
driven lattice gas
end-to-end distance
is a constant depending on r,
the afﬁnity mRNA-ribosome,…

13.
The initiation rate α is therefore length-dependent
(via “recycling” and ﬁnite-size effects)
• Fix a tentative initiation rate
• Simulate the system and extract J and R
• Compute the initiation rate
• Compare to the tentative one
J
We develop a self-consistent method to compute the
initiation rate

23.
The method: we simulated the translation in WT and
sup70-65 mutant to perform an in silico genetic screen
sensitive genesinsensitive
genes

24.
The predicted targets of tRNAGln
CUG regulation are
conﬁrmed by experiments
54% relative to WT control 103% relative to WT control
predicted to be sensitive predicted to be insensitive

25.
We used constitutively active mutants of the Gcn2
protein kinase to decrease the initiation
Gcn2 reduces (globally) the translation initiation rate via the
phosphorylation of the essential translation initiation factor eIF2-α
We tested our hypothesis on a gene (FAR7)
Also, we observed a signiﬁcant (almost 2-fold) shift in the
population away from chains and towards single cells
initiation rate
mutant/WT
translationrate
model

26.
Conclusions
• Initiation might be the origin of the ribosome density/
mRNA length dependence
• Elongation can be used to regulate gene expression
through the tuning of single-codon elongation rates
• Both initiation and elongation can be limiting steps
of translation

27.
Further perspectives
• How to independently study and modulate initiation
and elongation?
…undergoing experiments…

29.
The relative positioning of codons (elongation)
affects translational efﬁciency
Shufﬂing synonymous codons does not affect the ﬁnal product
(aa-sequence) and keeps the same codon usage
(codon used in a sequence).
original
synonymous

35.
Conclusions
• Finite-size effects are relevant in translation
• The three-dimensional conformation of the
polysome might enhance initiation (ribosome
“recycling”)
• The selﬁsh mRNA: is recycling a way to build up a
personal pool of ribosomes?